Resolved versus uncontrolled inflammation: A mathematical model to decipher the role of innate immunity

Understanding the impact of neutrophils and macrophages in the dynamic outcome of resolution vs uncontrolled response is still an open debate. Here, we develop a mathematical model that describe the dynamic of the innate immune response after acute damage. Our model includes all the described processes that mediate this response, including the regulatory mechanisms carried out by type 2 macrophages. Additionally, we estimate the resolution indices to quantify the efficiency of resolution mechanisms by controlling the initial expansion of neutrophils and/or the subsequent contraction kinetics of the cell response. We predict that the partial reduction of neutrophil influx and the increase of type 1 macrophage-mediated efferocytosis rate are the best strategies to control the neutrophil initial expansion. On the other hand, the partial reduction of type 1 macrophage cell influx or the increase of neutrophil apoptosis rate are predicted as good strategies to accelerate the neutrophils decay during the contraction phase of the response.